Mesothelial cells (MCs) cover the surface of visceral organs and the parietal walls of cavities, and they synthesize lubricating fluids to create a slippery surface that facilitates movement between organs without friction. Recent studies have indicated that MCs play active roles in liver development, fibrosis, and regeneration. During liver development, the mesoderm produces MCs that form a single epithelial layer of the mesothelium. MCs exhibit an intermediate phenotype between epithelial cells and mesenchymal cells. Lineage tracing studies have indicated that during liver development, MCs act as mesenchymal progenitor cells that produce hepatic stellate cells, fibroblasts around blood vessels, and smooth muscle cells. Upon liver injury, MCs migrate inward from the liver surface and produce hepatic stellate cells or myofibroblast depending on the etiology, suggesting that MCs are the source of myofibroblasts in capsular fibrosis. Similar to the activation of hepatic stellate cells, transforming growth factor β induces the conversion of MCs into myofibroblasts. Further elucidation of the biological and molecular changes involved in MC activation and fibrogenesis will contribute to the development of novel approaches for the prevention and therapy of liver fibrosis.
Epithelial Cells/*physiology ; Epithelium/metabolism ; Hepatic Stellate Cells/*physiology ; Humans ; Liver/*cytology/injuries/*physiology ; Liver Cirrhosis/etiology/prevention & control ; Liver Regeneration/*physiology ; Mesenchymal Stromal Cells/physiology ; Myofibroblasts/physiology

OBJECTIVETo observe the effect of D-galactosamine (D-GaIN) and lipopolysaccharide (LPS) on liver tissue regeneration and repair in mice following liver injury induced by partial hepatectomy.

METHODSA total of 40 male BALB/c mice were randomly assigned into 2 equal groups to receive intraperitoneal injections of D-GaIN (500 mg/kg) plus LPS (50 µg/kg, given 1 h later) or two doses of saline 24 h prior to 1/3 hepatectomy. The liver weight/body weight (LW/BW) ratio and liver regeneration rate were observed at different time points after partial hepatectomy. Liver cell injury was assessed using HE staining, hepatocyte proliferation evaluated with BrdU staining, and the oval cell proliferation observed with immunohistochemistry.

RESULTSIn mice receiving saline injection, the liver volume was nearly restored 9 days after partial hepatectomy, while in mice with D-GaIN and LPS injections, the liver failed to recover the normal volume even at 14 days, showing a significant difference in the liver regeneration rate between them [(22.6∓105.93)% vs (9.49∓32.55)%, P<0.001]. Significant degenerative changes of the hepatic cells were found in D-GaIN/LPS-treated group, while only mild inflammatory reaction was observed in saline-treated group after partial hepatectomy. Obvious hepatocyte proliferation was observed at day 7 in saline-treated group but not in D-GaIN/LPS-treated group. Oval cell proliferation in the portal area occurred 3 days after partial hepatectomy in D-GaIN/LPS-treated group.

CONCLUSIOND-GaIN and LPS can obviously inhibit hepatocyte regeneration after liver injury in mice. D-GaIN and LPS combined with partial hepatectomy can induce oval cell proliferation.

Animals ; Cell Proliferation ; drug effects ; Galactosamine ; pharmacology ; Hepatectomy ; methods ; Lipopolysaccharides ; pharmacology ; Liver ; cytology ; injuries ; physiopathology ; Liver Regeneration ; drug effects ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Stem Cells ; cytology